Pharmaceutical Impurity Testing Services

In the manufacturing process of biopharmaceuticals, it is possible to introduce process-related impurities into the final product at various stages. These impurities may come from upstream production processes such as cell substrate or cell culture, or from downstream processes and disposable bioprocessing systems. According to the current regulatory guidance of FDA, a new biopharmaceutical product should be conducted to identify its impurities and control them at a certain level. Therefore, analysis of process-related impurities is critical to biopharmaceutical development.

Organic impurities are derived from the process of pharmaceutical synthesis and degradation of APIs and drugs. The impurities introduced by the synthesis method are derived from raw materials, intermediates, reagents, ligands and catalysts used in chemical synthesis, as well as by-products from chemical synthesis. They may be volatile or non-volatile substances. The US Pharmacopoeia general chapters <466> and <1086> have established relevant requirements for the testing of organic impurities.

Residual solvents in pharmaceuticals refer to organic volatile compounds that are used in the manufacture of drug substance, excipients, and formulations, but are not completely removed during the process. In the drug substance synthesis process, selecting an appropriate solvent can increase the yield or determine the properties of the drug, such as crystal form, purity, dissolution rate, etc. Therefore, organic solvents are essential and very critical substances in drug synthesis reactions. When the residual solvent level contained in the drug is higher than the safe value, it will cause harm to the human body or the environment.

Pharmaceutical elemental impurities analysis is important for the commercialization, stability studies and clinical trials of pharmaceuticals. In some cases, the level of impurities below the toxicity threshold will have a significant impact on the properties of the drug, however, elemental impurities may not provide any benefit during the patient's treatment, so the elemental impurity content of the drug should be controlled at acceptance limits. ICH Q3D provides a guideline for the assessment of the toxicity of elemental impurities, permitted daily exposure (PDE) and control of the level of elemental impurities in the pharmaceutical. The USP <232> and <233> also sets new standards and methods for the control of element impurities in pharmaceutical.

Genotoxic compounds cause gene mutations and/or chromosomal rearrangements that damage DNA through different mechanisms and involve all types of DNA damage, including mutagenicity. Mutagenicity, on the other hand, is specifically involved in mutation induction at the gene and chromosome levels. The genotoxic impurities in pharmaceutical industry constitute an important class of genotoxic compounds. From a safety point of view, genotoxic impurities require more attention, risk assessment and control.

As one of the indispensable links in the production of pharmaceuticals, packaging materials play an important role in the quality of pharmaceuticals. The extractables and leachables produced by the packaging materials during long-distance transportation and long-term storage can become impurities in the pharmaceuticals and directly affect the safety and stability of the products. At present, the risk that the leachales in packaging and process equipment may cause harm to patients has been widely concerned. These hazards may directly affect the patient due to the safety of the leachate itself or the incompatibility of the drug formulation with certain leachables. Therefore, the identification and quantification of these harmful extractable and leachable impurities is essential.